The beneficial roles of insulin and parathyroid hormones in the treatment of experimentally induced diabetic osteoporosis in female rats: bone mineral density, morphometric and histological studies

Background: Diabetes mellitus (DM) and osteoporosis are two frequent medical conditions with an increasing prevalence in elderly people and are responsible for large number of incurable fractures. This study is designed experimentally in female rats in order to determine whether combined treatment of insulin and parathyroid hormone (PTH) enhances the reversibility of the osteoporotic changes that occurred in streptozotocin (STZ)-induced DM. Materials and methods: In this study, 30 adult female rats aged 3 months were used, they were randomly divided into: control group (6 rats) and diabetes group (24 rats), in which experimental DM was induced by i.p. injection of a single dose of STZ (60 mg/kg/body weight). Diabetic group was further divided into four subgroups (6 rats each): non-treated diabetic, insulin-treated (8–12 units s.c./day of Humalin U-40), PTH-treated (6.0 μg s.c./kg/day) and combined insulin and PTH-treated subgroups. All tested groups were assessed for body weight, food and water consumptions. Results: At the end of the experimental period, the bone mineral density (BMD) was measured for all rats of different groups; then the rats were sacrificed and blood samples were collected for measuring glucose, alkaline phosphatase and osteocalcin levels. Right femora were dissected out and subjected to measurement of diameter of neck and shaft, length of shaft, and weight. Then the femora specimens were processed and stained with haematoxylin and eosin for histological study. The results showed that there was a statistically significant, decrease in BMD, increase in the level of alkaline phosphate, and decrease in the level of osteocalcin in rats in diabetic group compared with other groups; these parameters improved in other groups, especially in diabetes/insulin/PTH group. The rats in diabetic group showed statistically significant decrease in neck and shaft diameters and weight of femur bone compared with other groups, while rats in diabetes/insulin/PTH group showed a significant improvement of these parameters. In diabetic group, there were different histopathological changes in cortical bone and Haversian canals, which improved in other groups, especially in rats in diabetes/insulin/PTH group. Conclusions: The untreated DM resulted in dramatic reduction in BMD and morphometric parameters. Treatment with insulin ameliorated these effects to some extent, while PTH co­-treatment had a more positive effect. The combination of PTH and insulin resulted in stronger improvement of all parameters to approximately like those of control rats

Influencia del tratamiento con microondas sobre la estabilidad del aceite de oliva.

The fruits of Picual and Shemlalli olive cultivars were exposed to microwaves generated from an oven at low and moderate power settings for 3, 6, 9 and 12 min. The physicochemical constants and fatty acid composition of the olive oil samples extracted from nonmicrowaved and microwaved fruits were determined. The data demonstrated that microwaves did not alter the values of the above mentioned parameters compared with the oil extracted from nonmicrowaved fruits. Quality assurance tests (acid, peroxide and TBA values) elucidated that microwaves generally increased the olive oil stability of Picual and Shemlalli cultivars during storage. In addition, microwaves generated from oven at moderate power setting for 12 min. exhibited an antioxidant power on olive oil equivalent to that possessed by BHT at 200 ppm.Aceitunas de las variedades Picual y Shemlalli fueron expuestas a una fuente de microondas generadas en un horno a potencia baja y moderada durante 3, 6, 9 y 12 minutos. Se determinaron las constantes físico-químicas y la composición en ácidos grasos de muestras de aceite de oliva extraído de aceitunas irradiadas y no irradiadas con microondas. Los datos demostraron que la irradiación con microondas no altera los valores de los parámetros antes mencionados si se compara con el aceite extraído de aceitunas no irradiadas. Los tests de garantía de calidad (índice de acidez, índice de peróxido y TBA) mostraron que la irradiación con microonda aumentó la estabilidad del aceite de oliva de las variedades Picual y Shemlalli durante su almacenamiento. En suma, la irradiación con microondas generadas en horno a potencia moderada durante 12 minutos produce un poder antioxidante sobre el aceite de oliva equivalente al que se obtuvo con el BHT a 200 ppm

Symptomatic Uncomplicated Diverticular Disease (SUDD): Practical Guidance and Challenges for Clinical Management

Symptomatic Uncomplicated Diverticular Disease (SUDD) is a syndrome within the diverticular disease spectrum, characterized by local abdominal pain with bowel movement changes but without systemic inflammation. This narrative review reports current knowledge, delivers practical guidance, and reveals challenges for the clinical management of SUDD. A broad and common consensus on the definition of SUDD is still needed. However, it is mainly considered a chronic condition that impairs quality of life (QoL) and is characterized by persistent left lower quadrant abdominal pain with bowel movement changes (eg, diarrhea) and low-grade inflammation (eg, elevated calprotectin) but without systemic inflammation. Age, genetic predisposition, obesity, physical inactivity, low-fiber diet, and smoking are considered risk factors. The pathogenesis of SUDD is not entirely clarified. It seems to result from an interaction between fecal microbiota alterations, neuro-immune enteric interactions, and muscular system dysfunction associated with a low-grade and local inflammatory state. At diagnosis, it is essential to assess baseline clinical and Quality of Life (QoL) scores to evaluate treatment efficacy and, ideally, to enroll patients in cohort studies, clinical trials, or registries. SUDD treatments aim to improve symptoms and QoL, prevent recurrence, and avoid disease progression and complications. An overall healthy lifestyle – physical activity and a high-fiber diet, with a focus on whole grains, fruits, and vegetables – is encouraged. Probiotics could effectively reduce symptoms in patients with SUDD, but their utility is missing adequate evidence. Using Rifaximin plus fiber and Mesalazine offers potential in controlling symptoms in patients with SUDD and might prevent acute diverticulitis. Surgery could be considered in patients with medical treatment failure and persistently impaired QoL. Still, studies with well-defined diagnostic criteria for SUDD that evaluate the safety, QoL, effectiveness, and cost-effectiveness of these interventions using standard scores and comparable outcomes are needed

Modest agreement between magnetic resonance and pathological tumor regression after neoadjuvant therapy for rectal cancer in the real world.

Magnetic resonance imaging (MRI) is routinely used for preoperative tumor staging and to assess response to therapy in rectal cancer patients. The aim of our study was to evaluate the accuracy of MRI based restaging after neoadjuvant chemoradiotherapy (CRT) in predicting pathologic response. This multicenter cohort study included adult patients with histologically confirmed locally advanced rectal adenocarcinoma treated with neoadjuvant CRT followed by curative intent elective surgery between January 2014 and December 2019 at four academic high-volume institutions. Magnetic resonance tumor regression grade (mrTRG) and pathologic tumor regression grade (pTRG) were reviewed and compared for all the patients. The agreement between radiologist and pathologist was assessed with the weighted k test. Risk factors for poor agreement were investigated using logistic regression. A total of 309 patients were included. Modest agreement was found between mrTRG and pTRG when regression was classified according to standard five-tier systems (k = 0.386). When only two categories were considered for each regression system, (pTRG 0-3 vs pTRG 4; mrTRG 2-5 vs mrTRG 1) an accuracy of 78% (95% confidence interval [CI] 0.73-0.83) was found between radiologic and pathologic assessment with a k value of 0.185. The logistic regression model revealed that "T3 greater than 5 mm extent" was the only variable significantly impacting on disagreement (OR 0.33, 95% CI 0.15-0.68, P = .0034). Modest agreement exists between mrTRG and pTRG. The chances of appropriate assessment of the regression grade after neoadjuvant CRT appear to be higher in case of a T3 tumor with at least 5 mm extension in the mesorectal fat at the pretreatment MRI

Misbehaviour of XIST RNA in Breast Cancer Cells

A role of X chromosome inactivation process in the development of breast cancer have been suggested. In particular, the relationship between the breast cancer predisposing gene BRCA1 and XIST, the main mediator of X chromosome inactivation, has been intensely investigated, but still remains controversial. We investigated this topic by assessing XIST behaviour in different groups of breast carcinomas and in a panel of breast cancer cell lines both BRCA1 mutant and wild type. In addition, we evaluated the occurrence of broader defects of heterochromatin in relation to BRCA1 status in breast cancer cells. We provide evidence that in breast cancer cells BRCA1 is involved in XIST regulation on the active X chromosome, but not in its localization as previously suggested, and that XIST can be unusually expressed by an active X and can decorate it. This indicates that the detection of XIST cloud in cancer cell is not synonymous of the presence of an inactive X chromosome. Moreover, we show that global heterochromatin defects observed in breast tumor cells are independent of BRCA1 status. Our observations sheds light on a possible previously uncharacterized mechanism of breast carcinogenesis mediated by XIST misbehaviour, particularly in BRCA1-related cancers. Moreover, the significant higher levels of XIST-RNA detected in BRCA1-associated respect to sporadic basal-like cancers, opens the possibility to use XIST expression as a marker to discriminate between the two groups of tumors

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types